The present invention relates to a tablet production method and a tablet, specifically to a tablet production method wherein molding material is hardly adhered on a punch and a die of a tabletting machine so that material can be continuously tabletted for a long time and disintegration time and hardness of produced tablet is the same as that of a tablet produced by an internal lubricant method and to a newly constructed tablet which can be produced by such a method.
A tablet is a very useful pharmaceuticals for carrying and dosing and is easy to be taken for an elder person or a patient because it doesn""t float on the water when dosing with water. Further, it has many advantages such that production cost of a tablet can be held down. Therefore, it is a most multipurpose dosage form for internal application and oral application.
Such a tablet is generally produced by a compression method.
However, when a tablet is produced by a compression method, there have been problems such that molding material is adhered on the punch and the dies of the tabletting machine to cause gride between the punch and the dies and sticking, capping, and laminating are apt to be caused.
In order to solve such problems, lubricant such as magnesium stearate, lauryl sodium sulphate, talc and so on are mixed in the molding material to be tabletted other than active component and diluting agent and the mixture is compressed to obtain a tablet so as to prevent that molding material to be tabletted is apt to attach on the punches and dies and gride between the punch and die is apt to be caused, to execute smooth tabletting, and to prevent defective goods (hereinafter, this tablet production method is called as xe2x80x9can internal lubricant methodxe2x80x9d).
On the other hand, it is advisable that adequate amount of lubricant is attached on the surfaces of the punches, the dies, and a tablet in order to prevent adhering of the molding material to be tabletted on the punches and the dies of the tabletting machine. Lubricant isn""t required to be contained in the tablet.
Based on these idea, there is a so called external tablet spraying method disclosed in for example JP-B-41-11273, JP-A-56-14098, and JP-A-7-124231 as a technique wherein the molding material to be tabletted is prevented from adhering on the punches and the dies of the tabletting machine while tabletting and the produced tablet is prevented from causing sticking and so on.
FIG. 7 schematically shows the procedures of the prior tablet production method disclosed in JP-B-41-11273.
According to this method, lubricant L is sprayed by air pressure from a spray nozzle 55 to a surface (lower surface) 53s of an upper punch 53 and a surface (upper surface) 54s of a lower punch 54 as shown in FIG. 7(a). Then, molding material m is charged in a die 51 provided for a rotary table 52 in the procedure shown in FIG. 7(b). Further, the molding material m is compressed to produce a tablet by means of the upper punch 53 of which surface (lower surface) 53s is applied with lubricant and the lower punch 4 of which surface (upper surface) 54s is applied with lubricant as shown in FIG. 7(c).
FIG. 8 schematically shows the procedures of the prior tablet production method disclosed in JP-A-56-14098.
According to this method, lubricant L is sprayed in a spray 56 provided above a die 51 of a rotary table 52 as shown in FIG. 8(a).
Then, lubricant L is placed on a surface (upper surface) 54s of a lower punch 54 as shown in FIG. 8(b). Compressed air is sprayed against the lower punch 54 from a nozzle 58 provided in a spraying chamber 57 which is provided separately from the spray 56. The lubricant L on the lower punch 54 is blown to be dispersed and the dispersed lubricant L is attached on a surface (inner wall) 51s of the die 51 and the surface (lower surface) 53s of the upper punch 53 as shown in FIG. 8(c). Accordingly, molding material (not shown) is compressed to produce a tablet by means of the die 51, the upper punch 53, and the lower punch 54 of which surface (inner wall) 51s, the surface (lower surface) 53s, and the surface (upper surface) 54s are lubricated.
However, according to the production methods described in JP-B-41-11273 and JP-A-56-14098, it has been impossible to apply lubricant L uniformly and stably on the surface (inner wall) 51s of the die 51, the surface (lower surface) 53s of the upper punch 53, and the surface (upper surface) 54s of the lower punch for a long time of tabletting. Therefore, they has problem such that they can""t be executed as an industrial production method.
The tablet production method disclosed in Jp-A-7-124231 has been proposed by the present inventors in order to solve the above-mentioned problems.
FIG. 9 schematically shows the procedures of the tablet production method disclosed in JP-A-7-124231.
According to this method, a tabletting machine in which a pulsating vibration air generation means 67 is connected above the die 51 before a step for charging molding material in the die 51 and a spraying chamber 58 having a spray nozzle 59 for spraying lubricant L is provided is prepared.
Then when the die 51, the upper punch 53, and the lower punch 54 come to a place where the spraying chamber 58 is provided by rotating the rotary table 52, pulsating vibration air is generated in the spraying chamber 58 by driving the pulsating vibration air generation means 67 and the lubricant L is sprayed from the spray nozzle 59 so as to attach on the surface (inner wall) 51s of the die 51, the surface (lower surface) 53s of the upper punch 53, and the surface (upper surface) 54s of the lower punch 54, as shown in FIG. 9(a).
As shown in FIG. 9(b), molding material is charged in the die 51.
Thereafter, molding material m is compressed to produce a tablet by means of the upper punch 53 and the lower punch 54 of which surfaces (lower surface 53s and upper surface 54s) are lubricated.
According to the production method disclosed in JP-A-7-124231, lubricant L can be uniformly and stably applied on the dies 51 and the punches 53, 54 by pulsating vibration air in a step of applying lubricant L so that material m is prevented from sticking on the punches 53, 54 and the die 51 and material can be continuously tabletted smoothly and stably for a long time, comparing to the production methods disclosed in JP-B-41-11273 and JP-A-56-14098.
However, according to the methods in JP-B-41-11273, JP-A-56-14098, and JP-A-7-124231, as lubricant L isn""t included in a tablet, there has been problems wherein property is differed such that disintegration time becomes fast and hardness becomes high, or absorption speed of active component into body is changed.
The present invention is proposed to solve the above-mentioned problems. The object of the invention is to provide a method for producing tablet wherein molding material doesn""t cause sticking and so on for the punches and the dies of the tabletting machine, tabletting can be continuously executed stably for a long time, it can be executed as an industrial tabletting method, and properties of the produced tablet such as disintegration time and hardness and absorption speed of active component into body don""t differ from a tablet produced by a normal internal lubricant method. And another object of the present invention is to provide a newly constructed tablet produced according to this tablet production method.
According to the method for producing tablet described in claim 1, a tablet including active component, diluting agent, and lubricant is produced by means of a tabletting machine provided with punches and dies, comprising steps of; preparing molding material including active component, diluting anent, and a part of lubricant; applying most of remaining amount of the lubricant on a surface of the punch and a surface of the die; and tabletting the molding material by means of the punches on which surfaces the lubricant is applied and the die on which surface the lubricant is applied.
The term xe2x80x9cdiluting agentxe2x80x9d in this specification means medicinal additive excluding lubricant. Namely it means that the term xe2x80x9cdiluting agentxe2x80x9d may include excipient used for shaping a tablet (formation), supplement such as solubilizing agent, solubilizer, buffering agent, hardening agent, binder and so on other than lubricant, adjuvant such as antioxidant, preservative, aroma, sweetening agent, colorant, and so on if required.
Several kinds of lubricant can be used for the tablet production method of the present invention. Lubricant isn""t specifically limited, for example, there are stearate acid metal salt (magnesium stearate, calcium stearate and so on), stearic acid, sodium lauryl sulfate, sodium lauryl magnesium, powdered gum arabic, carnauba wax, anhydrous silicic acid, magnesium oxide, silic acid hydrate, boric acid, fatty acid sodium salt, leucine, and so on which have been commonly used. One of them may be used solely or more than two of them may be combined.
According to the tablet production method of the present invention, the used amount of lubricant per a tablet is preferably adjusted to be almost the same as the lubricant amount used in an internal lubricant method.
In this specification, the term xe2x80x9cpunchesxe2x80x9d generally means a pair of an upper punch and a lower punch and xe2x80x9cpunch surfacesxe2x80x9d means a surface of an upper punch and a surface of a lower punch when punch means a pair of an upper punch and a lower punch.
Also the term xe2x80x9cdie surfacexe2x80x9d in this specification means an inner circumferential wall of a die above an upper surface of a lower punch when the lower punch is inserted in a predetermined position in the die.
Means for applying the remaining amount of lubricant on the punch surfaces and die surface isn""t particularly limited. Means disclosed in JP-B-41-11273, JP-B-48-20103, JP-A-56-14098, JP-A-59-205970, JP-A-4-295366, and JP-A-7-124231 may be used.
The method described in claim 2 concretely suggests a preferable step for applying most of the remaining amount of lubricant on the punch surfaces and the die surface.
According to the tablet production method in claim 2, in the method in claim 1, the step of applying most of remaining amount of the lubricant on the punch surfaces and the die surface is provided with a step of housing the punches and the die in a spraying chamber, and a step of spraying the most of remaining amount of lubricant while dispersing in the air in the spraying chamber.
As for the size of the spraying chamber, it is almost the same as or a little larger than the diameter of the die and also has a height for housing at least the lower surface of the upper punch positioned above the die.
Air used for spraying lubricant in the spraying chamber may be steady pressure air or pulsating vibration air.
According to the method as set forth in claim 3, in the method in claim 2, the step of spraying most of the remaining amount of lubricant in the spraying chamber is a step of spraying most of the remaining amount of lubricant while dispersing in positive steady pressure air.
The term xe2x80x9csteady pressure airxe2x80x9d in this specification means air of which pressure is hardly changed.
According to the method as set forth in claim 4, in the method in claim 2, the step of spraying most of the remaining amount of lubricant in the spraying chamber is a step of spraying most of the most of the remaining amount of lubricant while dispersing in positive pulsating vibration air.
xe2x80x9cPulsating vibration airxe2x80x9d in this specification means air of which pressure changes with time.
xe2x80x9cPositive pressurexe2x80x9d in this specification means that the pressure in the spraying chamber is higher than atmosphere outside thereof.
xe2x80x9cPositive pulsating vibration airxe2x80x9d used in this invention includes both positive pulsating vibration air of which peak and valley are positive and positive pulsating vibration air of which peak is positive and valley is atmospheric pressure.
According to the method as set forth in claim 5, in the method in claim 1, the step of applying most of the remaining amount of the lubricant on the punch surfaces and the die surface is comprised of the steps of; housing the punches and the die in the spraying chamber; and spraying most of the remaining amount of lubricant in the spraying chamber, and applying the lubricant on the punch surfaces and the die surface while generating pulsating vibration air in the spraying chamber.
Any pulsating vibration air having several periods and strengths may be used if it can forcibly diffuse lubricant particle sprayed in the spraying chamber by generating air vibration all around therein regardless that air pressure is positive or negative.
The term xe2x80x9cnegative pressurexe2x80x9d in this specification means that the pressure in the spraying chamber is lower than atmospheric pressure outside thereof.
xe2x80x9cNegative pulsating vibration airxe2x80x9d used in this invention includes both pulsating vibration air of which peak and valley are negative and pulsating vibration air of which peak is atmospheric pressure and valley is negative.
As such pulsating vibration air varies depending on the size and shape of the punches and the dies of the tabletting machine, the size and shape of the spraying chamber, attachment method of the spraying means, property of active component, and so on, it can""t be generally defined so that it is defined based on experiments.
The method described in claim 6 defines the ratio of the lubricant amount included in a tablet and the lubricant applied on the punch surfaces and the die surface. It is controlled that the part of lubricant contained in the molding material as set forth in claims 1-5 is greater than or equal to about 60 weight percent and less than or equal to about 99.99 weight percent for the entire amount of lubricant used for a tablet, and the most of the remaining amount of lubricant is greater than or equal to about 0.01 weight percent and less than or equal to about 40 weight percent for the entire amount of lubricant used for a tablet.
The term xe2x80x9cthe entire amount of lubricant used for a tabletxe2x80x9d in this specification means the used amount (weight) of lubricant for one tablet included in molding material used when a tablet is produced according to an internal lubricant method.
When most of the remaining amount of lubricant to be sprayed in the spraying chamber exceeds 40 weight % of the entire amount of lubricant used for a tablet, phenomenon such that molding material is attached on the punches and the die to cause sticking on the produced tablet is reduced. However, it isn""t desirable because property and dynamic state such as absorption, and so on of the produced tablet differ from a tablet produced according to an internal lubricant method.
When most of the remaining amount of lubricant to be sprayed in the spraying chamber is less than 0.01 weight % of the entire amount of lubricant used for a tablet, it isn""t desirable because phenomenon such that molding material is adhered on the punches and the die to cause sticking on the produced tablet happens at a similar frequency of an internal lubricant method.
The method as set forth in claim 7 defines the ratio of the lubricant amount included in a tablet and the lubricant applied on the punch surfaces and the die surface. It is controlled that the part of lubricant contained in the molding material described in claims 1-5 is greater than or equal to about 80 weight percent and less than or equal to about 99.99 weight percent for the entire amount of lubricant used for a tablet, and the most of the remaining amount of lubricant is greater than or equal to about 0.01 weight percent and less than or equal to about 20 weight percent for the entire amount of lubricant used for a tablet.
When the ratio of lubricant is within the above-mentioned range, properties such as disintegration time and hardness and absorption dynamic state of the produced tablet don""t change comparing to a tablet produced according to an internal lubricant method.
The method described in claim 8 or claim 9 defines preferable entire using amount of lubricant.
According to the method as set forth in claim 8, the entire amount of lubricant used for a tablet in the claims 1-7 is almost the same as the entire amount used for a tablet produced by an internal lubricant method.
According to the method as set forth in claim 9, the entire amount of lubricant used for a tablet in claims 1-7 is greater than or equal to 0.01 weight percent and less than or equal to 5 weight percent for the entire weight of a tablet.
In the method described in claim 8 or 9, the amount of lubricant included in a tablet is almost the same as the entire amount of lubricant for a tablet used in an internal lubricant method. Accordingly, when the method described in claim 7 or 8 is used, a tablet of which properties such as disintegration time and hardness and absorption dynamic state don""t change comparing to a tablet produced according to an internal lubricant method can be produced.
The tablet described in claim 10 defines construction of a tablet produced according to the methods described in claims 1-9.
The tablet described in claim 10 includes lubricant therein, and at least a part of lubricant applied on punch surfaces and a die surface used for molding material is accreted to the surface of the tablet with pressure.
According to the prior internal lubricant method, as lubricant is added to the molding material to be mixed, lubricant is almost uniformly applied in and on a tablet produced according to the method.
On the other hand, according to the prior external lubricant spraying method, lubricant isn""t added to molding material and is applied on punch surfaces and a die surface. A tablet produced by this method doesn""t include lubricant therein and at least a part of lubricant applied on punch surfaces and a die surface at the time of tabletting is accreted with pressure only on the surface of a tablet.
On the other hand, the tablet described in claim 10 includes lubricant therein and further at least a part of lubricant applied on punch surfaces and a die surface at the time of tabletting is accreted with pressure only on the surface of the tablet. A layer including lubricant per unit volume greater than the lubricant per unit volume included in the tablet is formed at an outer area of the tablet.
As the tablet described in claim 10 includes lubricant therein, disintegration characteristic and elution characteristic are similar to that of a tablet produced by the prior internal lubricant method.
Therefore, the tablet described in claim 10 can effectively prevent tabletting problems (such as sticking) because physical properties such as disintegration time and hardness and absorption dynamic state into a body of the produced tablet don""t change comparing to a tablet produced by an internal lubricant method and also the lubricant density of the surface of the produced tablet is high.